Two autoimmune dseases, hemolytic anemia and systemic lupus erythematous (SLE), are under investigation. NZB mice develop serologic and pathologic manifestations of autoimmune hemolytic anemia at about 6 months of age. NZB/W F1 hybrids develop membranous lupus-like nephritis, interstitial nephritis in some and together with the appearance of immune complexes in choroid plexes from 5 to 6 months old. The short span of the murine diseases which resemble the human diseases makes it a perfect mode to study their pathogenetic mechanism, prophylaxis and therapy. The responsible antigens on the mouse erythrocyte membrane are being sought by immunochemical and immunoferritin methods in the study of autoimmune hemolytic anemia in the same way as have been applied to investigation of virus receptor substance, blood group antigens and structural proteins of erythrocytes of many species of animals and man. Immunofluorescence studies on the murine nephritis have shown that antibodies to host globulin, complement, denatured DNA and some viral antigens are localized in glomerular capillary walls and choroid plexes. Thus immune complexes may be implicated in the pathogenesis of this disease similar to SLE in man. Cytidine (C), 5 methyluridine (T), guanosine (G) and adenosine (A) will be separately conjugated with globulin (Gb) from NZ mice. NZB/W F1 mice under one month old will be treated with a mixture of the Gb-nucleoside conjugates. Other groups of animals will be given unconjugated Gb and unconjugated nucleosdes. Another control group will be untreated. The onset of proteinuria, nephrotic syndrome, survival time, histologic and immunofluorescence studies of the renal and other tissues will be used to test the effect of the treatment. The effect of interferon and cyclophosphamide will also be tested. It is hoped that the findings on the murine diseases may lead to an understanding of the corresponding human diseases in relation to their pathogenesis and treatment.